Field of the Invention
Provided herein are novel aerosol inhalation formulations of ondansetron for pulmonary delivery; and uses thereof in the reduction, elimination or prevention of nausea and vomiting associated with chemotherapy, radiation therapy and surgery. Also provided are methods to treat chemotherapy-induced nausea and vomiting (CINV), radiation-induced nausea and vomiting (RINV), and post-operative nausea and vomiting (PONV) using the inhalation formulations.
Description of the Related Art Including Information Disclosed Under 37 CFR 1.97 and 1.98
Cancer is one of the major causes of death in the modern world. Major therapies to treat cancers include chemotherapy, radiation therapy and surgery. Nausea and vomiting are among the most common side-effects of these treatments. Patients receiving highly emetogenic agents may postpone, or even refuse, potentially curative treatments. Increasing of blood level of serotonin and activation of the 5-HT3 receptors in the chemoreceptor trigger zone in the brain are believed to be related to the emetic responses to cancer treatments [Hornby, 2001].
Ondansetron is a 5-HT3 receptor antagonist used mainly as an antiemetic often following chemotherapy, radiation therapy and surgery. Ondansetron is believed to block 5-HT3 receptors in the chemoreceptor trigger zone [Cooke et al., 1994]. It is believed to reduce the activity of the vagus nerve, hence the compound deactivates the vomiting center in the medulla oblongata [Ye et al., 2001]. FIG. 1 shows the skeletal formula of ondansetron.
Currently, ondansetron is administered either through injection (slow IV or IM) or as oral tablets. Injection of ondansetron, although effective in reducing or preventing nausea and vomiting, is inconvenient, invasive and causes pain to the patients. Existing forms of oral ondansetron tablets can be difficult to swallow and may be undesirable to some patients requiring anti-emetic therapy, especially those patients who have severe nausea or vomiting.
Thus, there remains a need for new formulations and for novel methods to administer ondansetron. The formulations, and methods described herein are directed toward this end.